TRALI is a non-cardiogenic pulmonary edema occurring within 6 hours of transfusion. Donor antibodies (anti-HLA or anti-HNA) activate recipient neutrophils, which sequester in the pulmonary microvasculature. Activated neutrophils release reactive oxygen species, proteases, and neutrophil extracellular traps (NETs) that damage the alveolar-capillary membrane. This results in increased permeability pulmonary edema with protein-rich fluid flooding the alveoli. A two-hit model suggests that recipient factors (sepsis, surgery, massive transfusion) prime neutrophils, and donor antibodies deliver the second hit.